Comprehensive Analysis of Ferroptosis-Related Markers for the Clinical and Biological Value in Gastric Cancer

Gastric cancer is a highly malignant tumor with poor survival rate. Ferroptosis, a newly defined regulated cell death, is closely related to several tumors. Introduction of ferroptosis is promising for cancer treatments. However, the predictive role of ferroptosis in GC remains elusive. In this study, we screened the ferroptosis-related genes which were differentially expressed between normal and GC tissues. Then, based on these differentially expressed genes (DEGs), the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regressions were applied to construct the 10-gene prognostic signature (SP1, MYB, ALDH3A2, KEAP1, AIFM2, ITGB4, TGFBR1, MAP1LC3B, NOX4, and ZFP36) in TCGA training dataset. Based on the median risk score, all GC patients in TCGA training dataset and GSE84437 testing dataset were classified into a high- or low-risk group. GC patients in the low-risk group showed significantly higher survival possibilities than those in the high-risk group (P < 0.001). Combined with the clinical characteristics, the risk score was proven as an independent factor for predicting the OS of GC patients. Besides, the GC patients in the high- or low-risk group showed significantly different GO and KEGG functional enrichments, somatic mutation, fractions of immune cells, and immunotherapy response. Then, the expression levels of these genes in signature were further verified in the GC cell lines and our own GC samples (30-paired tumor/normal tissues). Furthermore, the effects of ferroptosis inducer Erastin on these 10 ferroptosis-related genes in GC cell lines were also explored in our study. In conclusion, our study constructed a prognostic signature of 10 ferroptosis-related genes, which could well predict the prognosis and immunotherapy for GC patients.